Abstract

Recently, it has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. However, little is known of the expression of TLR7 in basophils of AR. To explore the expression of TLR7 in basophils of AR, and influence of allergens on TLR7 expression. The expression levels of TLR7 in basophils of patients with AR were determined by flow cytometry, and the influence of allergens on TLR7 expression was examined by real time (q) PCR. The percentages of TLR7+CCR3+ cells (P < 0.001 and P = 0.011), TLR7+CD123+HLA-DR- cells (P = 0 .016 and P = 0.042) and TLR7+CCR3+CD123+HLA-DR- cells (P = 0.046 and P = 0.035) in blood granulocyte and mononucleated cell populations of the patients with AR were increased, respectively compared with HC subjects. TLR7 MFI on CCR3+ cells (P = 0.050 and P = 0.043), CD123+HLA-DR- cells (P < 0.001 and P = 0.002) and CCR3+CD123+HLA-DR- cells (P < 0.001 and P = 0.003) were enhanced compared with HC subjects. Allergens Der p1 and OVA provoked upregulation of TLR7 expression at both protein and mRNA levels and IL-13 production in KU812 cells. House Dust Mite extract (HDME), Artemisia sieversiana wild allergen extract (ASWE), IL-31, IL-33, IL-37, and TSLP provoked elevation of IL-6 release from KU812 cells following 2 h incubation period. The percentage of TLR7+ basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7.

Highlights

  • It has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions

  • The percentage of TLR7+ basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7

  • The results showed that percentages of TLR7+CCR3+cells in blood granulocyte (Fig 1Ba, 2A) and mononucleated cell (Fig 1Ca, 2B) populations of the patients with AR were increased by 15.4 and 5.3-fold, respectively, compared with healthy control (HC) subjects

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Summary

Introduction

It has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. Little is known about the expression of Toll-like receptor (TLR) in AR. A clinical trial study on the Swedish population with AR revealed that AZD8848 as TLR7 agonist resulted in up-regulation of Th1 cytokines/chemokines (CXCL10, TNFα, IL-6, IFNγ) and suppression of Th2 cell functions in a profile which results in an improvement of AR symptoms. Intranasal application of a TLR7 agonist GSK2245035 was reported to enhance expression of the Th1 cytokines and suppression of AR symptoms. Little is known of the expression of TLR7 in basophils in AR

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